scholarly journals Genetic architecture of age-related cognitive decline in African Americans

2016 ◽  
Vol 3 (1) ◽  
pp. e125 ◽  
Author(s):  
Towfique Raj ◽  
Lori B. Chibnik ◽  
Cristin McCabe ◽  
Andus Wong ◽  
Joseph M. Replogle ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Cognitive Decline ◽  
Genetic Risk ◽  
Genetic Architecture ◽  
Genetic Risk Factors ◽  
Cognitive Change ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
Shared Risk

Objective:To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs).Methods:We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS.Results:We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility.Conclusions:The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD.

Prevalence of age-related macular degeneration associated genetic risk factors and 4-year progression data in the Irish population

2018 ◽  
Vol 102 (12) ◽  
pp. 1691-1695 ◽  
Author(s):  
Emma Connolly ◽  
Maedbh Rhatigan ◽  
Aisling M O’Halloran ◽  
Katherine Alyson Muldrew ◽  
Usha Chakravarthy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Disease Progression ◽  
Genetic Risk ◽  
Risk Allele ◽  
Genetic Risk Factors ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Age Related ◽  
Soft Drusen

Background/aimsAge-related macular degeneration (AMD) is estimated to affect 196 million people >50 years old globally. Prevalence of AMD-associated genetic risk factors and rate of disease progression are unknown in Ireland.MethodsPrevalence of AMD-associated genetic risk variants, complement factor H (CFH) rs1061170, age-related maculopathy susceptibility 2 (ARMS2) rs10490924, component 3 (C3) rs2230199, complement factor B (CFB) rs641153 and superkiller viralicidic activity 2-like (SKIV2L) rs429608 and 4-year progression data in a population-representative cohort (The Irish Longitudinal study on Ageing (TILDA)) were assessed. 4473 participants ≥50 years were assessed. 4173 had no disease n=1843; 44% male and n=2330; 56% female, mean age 60±9.0, 300 had AMD n=136; 45% male and n=164; 55% female, mean age 64±9.0. A 4-year follow-up was undertaken with 66% of AMD cases attending. Progression and regression from early to late AMD were measured. Genetic association as indicators of disease and as predictors of progression were assessed by multinomial logistic regression.ResultsOlder age and the presence of CFH and ARMS2 risk alleles are two main risk factors associated with the prevalence of AMD in the TILDA cohort. 23% progressed to a higher grade of AMD. Carriers of CFH risk allele showed a strong association for disease progression. Heterozygosity for ARMS2 risk allele predicted progression to late AMD. 75% of those who progressed from early to late disease had soft drusen and hyperpigmentation at baseline.ConclusionsThe prevalence of risk-associated genes and 4-year progression rates of AMD in this Ireland cohort are comparable with other Caucasian populations. CFH Y402H is associated with disease progression, with soft drusen and hyperpigmentation as high-risk features.

scholarly journals A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome

2022 ◽  
Vol 13 ◽  
Author(s):  
Samuel Houle ◽  
Olga N. Kokiko-Cochran
Keyword(s):  
Risk Factors ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Genetic Risk ◽  
Traumatic Injury ◽  
Genetic Risk Factors ◽  
Post Injury ◽  
Immune Stress ◽  
Age Related

Increasing evidence demonstrates that aging influences the brain's response to traumatic brain injury (TBI), setting the stage for neurodegenerative pathology like Alzheimer's disease (AD). This topic is often dominated by discussions of post-injury aging and inflammation, which can diminish the consideration of those same factors before TBI. In fact, pre-TBI aging and inflammation may be just as critical in mediating outcomes. For example, elderly individuals suffer from the highest rates of TBI of all severities. Additionally, pre-injury immune challenges or stressors may alter pathology and outcome independent of age. The inflammatory response to TBI is malleable and influenced by previous, coincident, and subsequent immune insults. Therefore, pre-existing conditions that elicit or include an inflammatory response could substantially influence the brain's ability to respond to traumatic injury and ultimately affect chronic outcome. The purpose of this review is to detail how age-related cellular and molecular changes, as well as genetic risk variants for AD affect the neuroinflammatory response to TBI. First, we will review the sources and pathology of neuroinflammation following TBI. Then, we will highlight the significance of age-related, endogenous sources of inflammation, including changes in cytokine expression, reactive oxygen species processing, and mitochondrial function. Heightened focus is placed on the mitochondria as an integral link between inflammation and various genetic risk factors for AD. Together, this review will compile current clinical and experimental research to highlight how pre-existing inflammatory changes associated with infection and stress, aging, and genetic risk factors can alter response to TBI.

scholarly journals Association between plasma phospho-tau181 and cognitive change from age 73 to 82: Lothian Birth Cohort 1936

2021 ◽  
Author(s):  
Tyler S Saunders ◽  
Amanda Heslegrave ◽  
Declan King ◽  
Sarah Harris ◽  
Craig W Ritchie ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Cognitive Change ◽  
Synaptic Function ◽  
Blood Biomarker ◽  
Array Tomography ◽  
Age Related ◽  
Lothian Birth Cohort ◽  
Synapse Degeneration ◽  
Age Related Cognitive Decline ◽  
The Brain

INTRODUCTION: Plasma phospho-tau 181 (p-tau181) is a promising blood biomarker for Alzheimer's disease. However, its predictive validity for age-related cognitive decline without dementia remains unclear. Several forms of p-tau have been shown to contribute to synapse degeneration, but it is unknown whether p-tau181 is present in synapses. Here, we tested whether plasma p-tau181predicts cognitive decline and whether it is present in synapses in human brain. METHODS: General cognitive ability and plasma p-tau181 concentration were measured in 195 participants at ages 72 and 82. Levels of p-tau181 in total homogenate and synaptic fractions were compared with western blot (n=10-12 per group), and synaptic localisation was examined using array tomography. RESULTS: Elevated baseline plasma p-tau181 and increasing p-tau181 over time predicted steeper general cognitive decline. We observe p-tau181 in neurites, presynapses, and post-synapses in the brain. DISCUSSION: Baseline and subsequent change in plasma p-tau181 may represent rare biomarkers of differences in cognitive ageing across the 8th decade of life and may play a role in synaptic function in the brain.

scholarly journals Plant-Based Dietary Patterns, Plant Foods, and Age-Related Cognitive Decline

2019 ◽  
Vol 10 (Supplement_4) ◽  
pp. S422-S436 ◽  
Author(s):  
Sujatha Rajaram ◽  
Julie Jones ◽  
Grace J Lee
Keyword(s):  
Risk Factors ◽  
Cognitive Decline ◽  
Dietary Patterns ◽  
Randomized Clinical Trials ◽  
Unsaturated Fatty Acids ◽  
Well Being ◽  
Neuroprotective Effects ◽  
Plant Foods ◽  
Age Related ◽  
Age Related Cognitive Decline

ABSTRACT The aging population is expanding, as is the prevalence of age-related cognitive decline (ARCD). Of the several risk factors that predict the onset and progression of ARCD, 2 important modifiable risk factors are diet and physical activity. Dietary patterns that emphasize plant foods can exert neuroprotective effects. In this comprehensive review, we examine studies in humans of plant-based dietary patterns and polyphenol-rich plant foods and their role in either preventing ARCD and/or improving cognitive function. As yet, there is no direct evidence to support the benefits of a vegetarian diet in preventing cognitive decline. However, there is emerging evidence for brain-health–promoting effects of several plant foods rich in polyphenols, anti-inflammatory dietary patterns, and plant-based dietary patterns such as the Mediterranean diet that include a variety of fruits, vegetables, legumes, nuts, and whole grains. The bioactive compounds present in these dietary patterns include antioxidant vitamins, polyphenols, other phytochemicals, and unsaturated fatty acids. In animal models these nutrients and non-nutrients have been shown to enhance neurogenesis, synaptic plasticity, and neuronal survival by reducing oxidative stress and neuroinflammation. In this review, we summarize the mounting evidence in favor of plant-centered dietary patterns, inclusive of polyphenol-rich foods for cognitive well-being. Randomized clinical trials support the role of plant foods (citrus fruits, grapes, berries, cocoa, nuts, green tea, and coffee) in improving specific domains of cognition, most notably frontal executive function. We also identify knowledge gaps and recommend future studies to identify whether plant-exclusive diets have an added cognitive advantage compared with plant-centered diets with fish and/or small amounts of animal foods.

Combined effects of genetic and non-genetic risk factors affect response to ranibizumab in exudative age-related macular degeneration

2014 ◽  
Vol 93 (6) ◽  
pp. e451-e457 ◽  
Author(s):  
Stefano Piermarocchi ◽  
Stefania Miotto ◽  
Davide Colavito ◽  
Alberta Leon ◽  
Tatiana Segato
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
Age Related Macular Degeneration ◽  
Combined Effects ◽  
Age Related

202 In African Americans, NOD2, SLC22A5 and ATG16L1 But Not Il23R or IRGM Are Genetic Risk Factors for Crohn's Disease

2009 ◽  
Vol 136 (5) ◽  
pp. A-38
Author(s):  
Ming-Hsi Wang ◽  
Toshihiko Okazaki ◽  
Kim L. Isaacs ◽  
James D. Lewis ◽  
Duane T. Smoot ◽  
...  
Keyword(s):  
Risk Factors ◽  
Crohn’S Disease ◽  
African Americans ◽  
Crohn's Disease ◽  
Genetic Risk ◽  
Genetic Risk Factors

scholarly journals Multiple distinct CHRNB3-CHRNA6 variants are genetic risk factors for nicotine dependence in African Americans and European Americans

Addiction ◽  
2014 ◽  
Vol 109 (5) ◽  
pp. 814-822 ◽  
Author(s):  
Robert C. Culverhouse ◽  
Eric O. Johnson ◽  
Naomi Breslau ◽  
Dorothy K. Hatsukami ◽  
Brooke Sadler ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Nicotine Dependence ◽  
Genetic Risk ◽  
Genetic Risk Factors ◽  
European Americans

scholarly journals Determining the Role of ApoE4 in Age-Related Cerebrovascular Decline

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 118-119
Author(s):  
Kate Foley ◽  
Peter Borchian ◽  
Dylan Garceau ◽  
Kevin Kotredes ◽  
Paul Territo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Transcriptional Profiling ◽  
Genetic Risk Factors ◽  
Expression Of Genes ◽  
Age Related ◽  
Age Dependent ◽  
Cerebrovascular Health ◽  
E4 Allele

Abstract Cerebrovascular decline occurs during aging and may be critical during prodromal phases of Alzheimer’s disease (AD). The E4 allele of apolipoprotein E (APOE4) is the greatest genetic risk factor for AD and decreased longevity and studies suggest APOE4 increases risk for age-dependent cerebrovascular damage. To study the relationship between APOE4 and age-related cerebrovascular decline, male and female C57BL/6J (B6) mice carrying combinations of APOE alleles including APOE4 (risk) and APOE3 (neutral), as well as B6 controls were assessed at a variety of ages from 4 to 24 mos for cognitive ability, biometrics and cerebrovascular health including i) PET/MRI using 64Cu-PTSM (perfusion) and 18F-FDG (metabolism), ii) transcriptional profiling and iii) immunofluorescence. Despite no cognitive decline, male APOE4 mice showed hypo-perfusion and hypo-metabolism by 12 mos, while female APOE4 mice showed an uncoupled hyper-perfusion and hypo-metabolism phenotype. Transcriptional profiling showed differential expression of genes involved in regulation of cerebral perfusion, glucose transportation and metabolism in APOE4 mice. An age-dependent blood brain barrier compromise was also apparent in the brains of female APOE4 mice. Physical activity reduces risk for human AD and our data shows exercise improves cerebrovascular health in mice. However, the effects to cerebrovascular health in individuals carrying genetic risk factors such as APOE4 are not known. To determine whether exercise can overcome APOE4-dependent cerebrovascular damage, APOE mice are being exercised from 2-4 and to 2-12 mos. Transcriptional profiling and immunofluorescence will determine whether the benefits of exercise to the cerebrovasculature are modulated by genetic risk factors such as APOE4.

Cognitive change before old age (11 to 70) predicts cognitive change after old age (70 to 82)

2021 ◽  
Author(s):  
Federica Conte ◽  
Judith Okely ◽  
Olivia Hamilton ◽  
Janie Corley ◽  
Danielle Page ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Old Age ◽  
Social Impact ◽  
Adult Life ◽  
Cognitive Change ◽  
Older Age ◽  
Growth Curve Models ◽  
Age Related ◽  
Lothian Birth Cohort ◽  
Age Related Cognitive Decline

Identifying predictors of cognitive decline within older age helps to understand its mechanisms and to identify those at greater risk. Here we examine how cognitive change from 11 to 70 years is associated with cognitive change within older age (70 to 82 years) in the Lothian Birth Cohort 1936 longitudinal study (N=1091 at recruitment). Using latent growth curve models, we estimate rates of change from age 70 to 82 in general cognitive ability (g) and in three cognitive domains: visuospatial, memory and processing speed. g accounted for 71.3% of interindividual change variance. Greater 11-70 cognitive gain predicted slower decline in g over 12 subsequent years (β = .163, p = .001), independently of cognitive level at age 70, and domain-specific change beyond g. These results contribute toward identifying people at higher risk of age-related cognitive decline. Age-related cognitive decline is a significant threat to the quality of life in older age. Its economic and social impact on society will increase together with the steadily rising life expectancy. How can we preserve cognitive health in older age? Researchers have made significant advances in identifying protective and risk factors. However, most studies focus on a limited age range, and cognitive change mechanisms are not yet completely understood. This work takes advantage of almost life-spanning longitudinal data to test if cognitive trajectory across childhood and adulthood can predict cognitive trajectories in older age. Our findings show that earlier change is associated with later change. Some factors related to individual differences in cognitive change might thus operate over much of the adult life course, and certainly before older age. This knowledge can help identify individuals at higher risk of decline and understand the mechanisms and factors responsible.

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